title: Docking studies towards exploring antiviral compounds against envelope protein of yellow fever virus.
abstract: Yellow fever is among one of the most lethal viral diseases for which approved antiviral therapies were yet to be discovered. Herein, functional assignment of complete YFV proteome was done through support vector machine. Major envelope (E) protein that mediates entry of YFV into host cell was selected as a potent molecular target. Three dimensional structure of the molecular target was predicted using Modeller9v7. The model was optimized in Maestro9.0 applying OPLS AA force field and was evaluated using PROCHECK, ProSA, ProQ and Profile 3D. The BOG pocket residues Val48, Glu197, Thr200, Ile204, Thr265, Thr268 and Gly278 were located in YFV E protein using SiteMap2.3. More than one million compounds of Ligandinfo Meta database were explored using a computational virtual screening protocol targeting BOG pocket of the E protein. Finally, ten top ranked lead molecules with strong binding affinity to BOG pocket of YFV E protein were identified based on XP Gscore. Drug likeliness and comparative bioactivity analysis for these leads using QikProp3.2 had shown that these molecules would have the potential to act as better drug. Thus, the 10 lead molecules suggested in the present study would be of interest as promising starting point for designing antiviral compound against yellow fever.
authors.affiliation: SVIMS Bioinformatics Centre, Department of Bioinformatics, SVIMS University, Tirupati, 517507, AP, India. svims.btisnet@nic.in
authors.forename: Amineni
authors.initials: A
authors.lastname: Umamaheswari
authors.forename: Manne Muni
authors.initials: MM
authors.lastname: Kumar
authors.forename: Dibyabhaba
authors.initials: D
authors.lastname: Pradhan
authors.forename: Hemanthkumar
authors.initials: H
authors.lastname: Marisetty
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry*; D001665:Binding Sites; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D020543:Proteome; D054852:Small Molecule Libraries; D012984:Software; D060388:Support Vector Machine; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D015005:Yellow fever virus / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D020543:Proteome; D054852:Small Molecule Libraries; D014759:Viral Envelope Proteins